Hypoxic-ischemic brain injury is a major problem in pediatric neurology and the most important neurological problem in the perinatal period. It accounts for more nonprogressive handicapping neurological disorders (e.g., movement disorders, spasticity) in children than any other type of brain injury. Neurotransmitter actions and residual imbalances may play major roles in the pathogenesis of acute injury and later sequelae. In spite of its clinical importance, very little is known about the effects of hypoxic-ischemic injury on transmitter systems in developing brain. Information about neurochemical changes in acute injury will help to find and test neuroprotective drugs to reduce damage. Knowledge of patterns of neuronal selective vulnerability and plasticity following injury will improve treatment and prevention of long-term morbidity. To study this problem in an animal model, hypoxic-ischemic injury has been produced in the neostriatum of immature rats. Histopathological examination reveals unilaterial reduction in striatal mass and status marmoratus. Injury produces a 70% reduction in ipsilaterial dopamine and behavioral evidence of dopamine neuronal damage. Using biochemical markers for neurotransmitter specific neurons and simple histologic techniques, the studies will characterize the selective effects of injury. Additional experiments will examine the ability of barbiturates to modify hypoxic-ischemic injury in this system. Use of transmitter markers to study a model which replicates features of the human disorder will greatly improve our understanding of this condition.